Research

Vasudha Salgotra is an expert in drug metabolism and pharmacokinetics (DMPK), and is a co-author on multiple peer-reviewed publications in the development of drug delivery and analytical biochemistry analysis of pharmaceutically relevant compounds. 

My research group focuses on translational pharmacokinetics, ADME, and drug metabolism. Students generate in vitro ADME data using NanoDrop and LC-MS and learn how these parameters inform drug development and, where applicable, PBPK modeling using PK-Sim to predict systemic exposure. In addition to wet lab projects, students also work on computational PBPK modeling projects based on literature-derived data.

Student Learning

Students gain experience in ADME assays, NanoDrop and LC-MS analysis, pharmacokinetic data interpretation, PBPK modeling, and scientific writing. By working across both experimental and computational projects, they develop a strong understanding of how data translates into real-world drug development decisions.

Why Study Drug Metabolism and Pharmacokinetics?

With modern advances in drug discovery and medicinal chemistry, the development of potent compounds in the present day is a fast paced and growing field. However, a major "make or break" point of many pharmaceutical entities between being successes in a laboratory to becoming clinically validated therapeutics that can make a difference in human health rests in what a small molecule or protein goes through once ingested and absorbed into the body, bloodstream, and periphery. 

At this point, the major challenges that a drug molecule or biologic must face include:

1. Having the right physical properties for optimal ABSORPTION - how much is actually uptaken into circulation vs. into cells?

2. Having the proper localization to result in optimal DISTRIBUTION - where in the body does the drug entity localize?

3. Being able to survive METABOLISM by our body's natural elimination mechanisms - what happens as the host target begins to degrade the drug?

4. Controlling the rate of EXCRETION by our body's clearance mechanisms - how quickly is a drug eliminated from systemic circulation? 

5. Minimizing off target TOXICITY - addressing a grand challenge of drug delivery requires elimination of off-target toxicity profiles.

*For a seminal review, please see Benedetti, et al.: "Drug metabolism and pharmacokinetics"

What tools does our lab use to study drug metabolism and pharmacokinetics (DMPK)?

The Salgotra Lab uses several state-of-the-art instrumental techniques to gain quantitative and precise insight into drug metabolism dynamics and to study chemical and biological stability and compatibility of drug compounds, spanning mass spectrometry and HPLC based assays to using computer modeling to predict DMPK properties.

Current Projects

Wet Lab Project---Food Effect and Exposure Prediction: ADME and PBPK Modeling of Apitolisib (Completed – Manuscript in Preparation)

This project characterizes the ADME profile of Apitolisib using hepatic microsomal stability, plasma protein binding, and physicochemical assessments, with analysis via NanoDrop and LC-MS. The data were integrated into a PBPK model in PK-Sim to simulate systemic exposure under fed and fasted conditions, providing insight into the impact of food on pharmacokinetics.

Wet Lab Project---Structure–PK Relationships: Comparative ADME and PBPK Analysis of Andrographolide Analogues (Ongoing)

This multi-group project compares andrographolide and its analogues (methoxy trityl, TBDPS, and methyl trityl) to understand how structural modifications influence pharmacokinetics. Students conduct hepatic microsomal stability, plasma protein binding, and physicochemical assays using NanoDrop and LC-MS. The TBDPS group has completed wet lab work and is preparing a manuscript, while other groups are ongoing. Experimental data are being used to develop PBPK models in PK-Sim to compare predicted systemic exposure.

Note: We are wokring on different analogues of Andrographolide and is considered a separate project. Some are in progress and some has not been started yet.

Online Project ---Mechanism-Based PBPK Modeling: Enhancing Apigenin Bioavailability Using Bioenhancers (Ongoing – Computational Project)

This project focuses on predicting the potential enhancement of Apigenin bioavailability using bioenhancers through PBPK modeling. Students conduct literature-based ADME research to identify metabolic pathways of Apigenin, including key enzymes involved in its metabolism. They also investigate how bioenhancers may inhibit these enzymes and reduce metabolic clearance. The collected data are used to build PBPK models in PK-Sim to simulate how enzyme inhibition could improve systemic exposure. This project emphasizes mechanistic understanding and the use of literature-derived inputs for modeling.

Online Project---Special Population Modeling: PBPK Simulation of GLP-1 Agonists in Pregnancy (Ongoing – Computational Project)

This project explores how physiological changes during pregnancy affect the pharmacokinetics of GLP-1 agonists. Students extract physiological parameters for pregnant populations from literature and modify key factors such as organ blood flow, plasma volume, and clearance processes within PK-Sim to represent pregnancy conditions. PBPK simulations are then used to compare systemic exposure between pregnant and healthy populations. This project highlights the importance of population-specific modeling in drug development and safety assessment.